Heterogeneity in genetic admixture across different regions of Argentina

The population of Argentina is the result of the intermixing between several groups, including Indigenous American, European and African populations. Despite the commonly held idea that the population of Argentina is of mostly European origin, multiple studies have shown that this process of admixture had an impact in the entire Argentine population. In the present study we characterized the distribution of Indigenous American, European and African ancestry among individuals from different regions of Argentina and evaluated the level of discrepancy between self-reported grandparental origin and genetic ancestry estimates. A set of 99 autosomal ancestry informative markers (AIMs) was genotyped in a sample of 441 Argentine individuals to estimate genetic ancestry. We used non-parametric tests to evaluate statistical significance. The average ancestry for the Argentine sample overall was 65% European (95%CI: 63–68%), 31% Indigenous American (28–33%) and 4% African (3–4%). We observed statistically significant differences in European ancestry across Argentine regions [Buenos Aires province (BA) 76%, 95%CI: 73–79%; Northeast (NEA) 54%, 95%CI: 49–58%; Northwest (NWA) 33%, 95%CI: 21–41%; South 54%, 95%CI: 49–59%; p<0.0001] as well as between the capital and immediate suburbs of Buenos Aires city compared to more distant suburbs [80% (95%CI: 75–86%) versus 68% (95%CI: 58–77%), p = 0.01]. European ancestry among individuals that declared all grandparents born in Europe was 91% (95%CI: 88–94%) compared to 54% (95%CI: 51–57%) among those with no European grandparents (p<0.001). Our results demonstrate the range of variation in genetic ancestry among Argentine individuals from different regions in the country, highlighting the importance of taking this variation into account in genetic association and admixture mapping studies in this population.     

Further characterization of agmatine binding to mitochondrial membranes: involvement of imidazoline I2 receptor

Agmatine, a divalent diamine with two positive charges at physiological pH, is transported into the matrix of liver mitochondria by an energy-dependent mechanism, the driving force of which is the electrical membrane potential. Its binding to mitochondrial membranes is studied by applying a thermodynamic treatment of ligand-receptor interactions on the analyses of Scatchard and Hill. The presence of two mono-coordinated binding sites S(1) and S(2), with a negative influence of S(2) on S(1), has been demonstrated. The calculated binding energy is characteristic for weak interactions. S(1) exhibits a lower binding capacity and higher binding affinity both of about two orders of magnitude than S(2). Experiments with idazoxan, a ligand of the mitochondrial imidazoline receptor I(2), demonstrate that S(1) site is localized on this receptor while S(2) is localized on the transport system. S(1) would act as a sensor of exogenous agmatine concentration, thus modulating the transport of the amine by its binding to S(2).     

Localizing FST outliers on a QTL map reveals evidence for large genomic regions of reduced gene exchange during speciation‐with‐gene‐flow

Populations that maintain phenotypic divergence in sympatry typically show a mosaic pattern of genomic divergence, requiring a corresponding mosaic of genomic isolation (reduced gene flow). However, mechanisms that could produce the genomic isolation required for divergence‐with‐gene‐flow have barely been explored, apart from the traditional localized effects of selection and reduced recombination near centromeres or inversions. By localizing F_ST outliers from a genome scan of wild pea aphid host races on a Quantitative Trait Locus (QTL) map of key traits, we test the hypothesis that between‐population recombination and gene exchange are reduced over large ‘divergence hitchhiking’ (DH) regions. As expected under divergence hitchhiking, our map confirms that QTL and divergent markers cluster together in multiple large genomic regions. Under divergence hitchhiking, the nonoutlier markers within these regions should show signs of reduced gene exchange relative to nonoutlier markers in genomic regions where ongoing gene flow is expected. We use this predicted difference among nonoutliers to perform a critical test of divergence hitchhiking. Results show that nonoutlier markers within clusters of F_ST outliers and QTL resolve the genetic population structure of the two host races nearly as well as the outliers themselves, while nonoutliers outside DH regions reveal no population structure, as expected if they experience more gene flow. These results provide clear evidence for divergence hitchhiking, a mechanism that may dramatically facilitate the process of speciation‐with‐gene‐flow. They also show the power of integrating genome scans with genetic analyses of the phenotypic traits involved in local adaptation and population divergence.     

Design of a bovine low-density SNP array optimized for imputation

The Illumina BovineLD BeadChip was designed to support imputation to higher density genotypes in dairy and beef breeds by including single-nucleotide polymorphisms (SNPs) that had a high minor allele frequency as well as uniform spacing across the genome except at the ends of the chromosome where densities were increased. The chip also includes SNPs on the Y chromosome and mitochondrial DNA loci that are useful for determining subspecies classification and certain paternal and maternal breed lineages. The total number of SNPs was 6,909. Accuracy of imputation to Illumina BovineSNP50 genotypes using the BovineLD chip was over 97% for most dairy and beef populations. The BovineLD imputations were about 3 percentage points more accurate than those from the Illumina GoldenGate Bovine3K BeadChip across multiple populations. The improvement was greatest when neither parent was genotyped. The minor allele frequencies were similar across taurine beef and dairy breeds as was the proportion of SNPs that were polymorphic. The new BovineLD chip should facilitate low-cost genomic selection in taurine beef and dairy cattle.     

A novel tetrahydrobenzoangelicin with dark and photo biological activity

The synthesis of 8,9,10,11-tetrahydro-5-(3-dimethylaminopropoxy)-4-methylbenzofuro[2,3-h]coumarin (5) is described. The new compound showed the ability to inhibit cell growth both upon UVA irradiation and in the dark. The investigation on the mechanism of action highlighted the capacity of 5 to covalently photoadd to thymine, as demonstrated by the isolation and characterization of the 4',5'-monoadduct. Furthermore, in the ground state 5 interferes with the topoisomerase II relaxation activity, suggesting that this enzyme could constitute a molecular target responsible for the dark antiproliferative effect.     

Inhibitors of sterol synthesis. Chromatography of acetate derivatives of oxygenated sterols

The separation of the acetate derivatives of a number of oxygenated sterols was achieved by medium pressure liquid chromatography on silica gel columns and by normal and reversed phase high performance liquid chromatography. We have explored the application of these chromatographic systems for the analysis of oxygenated sterols of plasma samples from two normal human subjects. The addition of highly purified [14C]cholesterol to plasma permitted the detection and quantitation of oxygenated sterols formed by autoxidation of cholesterol during processing of the samples. Special attempts to suppress autoxidation of cholesterol included the use of an all-glass closed system for saponification and extraction under argon followed by rapid removal of cholesterol from the polar sterols by reversed phase medium pressure liquid chromatography. Chromatographic analyses of the [3H]acetate derivatives of the polar sterols provided a sensitive approach for the detection and quantitation of the individual oxygenated sterols. Oxygenated sterols detected in plasma included cholest-5-ene-3 beta,26-diol, (24S)-cholest-5-ene-3 beta,24-diol, and cholest-5-ene-3 beta,7 alpha-diol. After correction for their formation by autoxidation of cholesterol during processing of the samples, very little or none of the following sterols were observed: cholest-5-ene-3 beta,7 beta-diol, 5 alpha,6 alpha-epoxy-cholestan-3 beta-ol, 5 beta,6 beta-epoxy-cholestan-3 beta-ol, and cholestane- 3 beta, 5 alpha,6 beta-triol, and the 25-hydroxy, 22R-hydroxy, 21-hydroxy, 20 alpha-hydroxy, and 19-hydroxy derivatives of cholesterol.     

Kinetics of T cell activation in acute and chronic forms of murine graft-versus-host disease

Induction of graft-vs-host disease (GVHD) in the parent-into-F1 model is dependent on the presence of T cells in the donor inoculum. Although in vivo activation of donor T cells in response to F1 alloantigens is thought to be critical to GVHD induction, direct evidence of activated donor T cells has been lacking in this model. In the present study, spleen cells from acute or chronic GVHD mice were studied for evidence of T cell activation at multiple intervals early after GVHD induction. Spleen cells from both acute and chronic GVHD mice exhibited striking elevations in spontaneous proliferation and IL-2 production, which were maximal 24 to 48 h after GVHD induction. Persistent lower levels of spontaneous in vitro activity were observed for spleen cells from mice tested 7 to 9 days after GVHD induction. In both forms of GVHD, increased spontaneous proliferation and IL-2 production were dependent on the presence of donor CD4+ T cells. These results strongly support the presence of activated donor T cells in vivo. Furthermore, these data imply that despite the significant differences in outcome, acute and chronic GVHD share a common early event.     

The potentiation of B lymphocyte responses through CD2/LFA-3 interactions involving erythrocytes is IL2 independent

The response of human B cells to pokeweed mitogen (PWM) stimulation is potentiated when autologous erythrocytes (E) are added to peripheral blood mononuclear cell (PBMC) cultures. This potentiation has been previously shown to be dependent on interactions between the CD2 molecule on T cells and the lymphocyte function-associated antigen 3 (LFA-3) expressed by autologous erythrocytes. Since in other experimental systems the activation of T cells by CD2/LFA-3 interactions has resulted in increased secretion of interleukin 2 (IL2), we were interested in studying the role of IL2 in PBMC cultures stimulated with PWM and autologous E. The addition of autologous E significantly depressed IL2 levels in PWM-stimulated PBMC cultures. This effect was not secondary to increased expression of IL2 receptors by activated cells, since the addition of anti-TAC antibodies did not result in a significant increase in measurable levels of IL2. The addition of anti-IL2 to PBMC failed to abrogate the potentiating effect of E and it actually further enhanced the production of IgM and IgG from cultures stimulated with PWM + E. These results suggest that the potentiation of B cell function induced by autologous E is not mediated by IL2, either directly or indirectly. It is possible that the effect of autologous E either is mediated by other interleukins or is dependent on cell-to-cell contact with directed release of IL2 and/or other lymphokines without detectable secretion to the extracellular compartment.     

Classification of the Sieversio montanae-Nardetum strictae in a cross-section of the Eastern Alps

The Sieversio montanae-Nardetum strictae is one of the most widespread plant communities in (sub-) alpine regions of the Alps. Our study examines the composition, ecology and distribution of this plant community in the Eastern Alps and addresses the issue of how the community is to be classified in the phytosociological system of Nardus-rich grasslands. Therefore, 357 vegetation relevés were taken from the literature and 115 from our own inventories were recorded from 2005 to 2007 in Western Austria (mostly Tyrol) and Northern Italy (mostly South Tyrol). Additionally, indicator values of Ellenberg and land-use information were used to help better interpret the ecological site conditions of the subgroups. The HCA revealed there the existence of four groups of the Sieversio montanae-Nardetum strictae, which were classified to subassociations: (1) typicum, (2) vaccinietosum, (3) trifolietosum pratensis, and (4) seslerietosum albicantis. Besides the specific plant composition, altitude specifies the first, land-use intensity the second and third, and the pH of the topsoil the fourth subassociation. For the Eastern Alps, the plant community of the Sieversio montanae-Nardetum strictae should now be reclassified in the order of Nardetalia and the class of Calluno-Ulicetea. Finally, this plant community can be further classified by using the four above-mentioned subassociations.